IMCY-0141 Safety and Efficacy in Multiple Sclerosis - ISEMIS Study

Summary

The IMCY-MS-001 study is a study to test a new experimental drug, IMCY-0141, for the treatment of Relapsing-Remitting Multiple Sclerosis (RR-MS). The pathophysiology of MS with known myelin autoantigens and T cell epitopes makes this disease a particularly attractive indication for development of an immunotherapeutic based on the Imcyse technology. Based on the unique mechanism of action of the drug, IMCY-0141 administered as early as possible after confirmation of the diagnosis may potentially switch-off the autoimmune process and limit the corresponding myelin destruction. Newly (recently) diagnosed patients will be targeted to tackle the disease at its onset. Before launching any efficacy studies, safety of IMCY-0141 in MS patients must be evaluated with a phase I, open-label, dose escalation clinical trial to evaluate the safety of three IMCY-0141 doses followed by a phase II, double-blind, randomized study with an adaptive design to determine if any IMCY-0141 dose(s) offer superior efficacy relative to placebo and to assess immune responses and biomarker data as potential early predictors of efficacy of IMCY-0141 in adults presenting with RR-MS.

Timeline

Start

2022-04-12

Primary completion

2025-05-23

Completion

2025-12-31

Publications

• Background Malek Abrahimians E, Carlier VA, Vander Elst L, Saint-Remy JM. MHC Class II-Restricted Epitopes Containing an Oxidoreductase Activity Prompt CD4(+) T Cells with Apoptosis-Inducing Properties. Front Immunol. 2015 Sep 2;6:449. doi: 10.3389/fimmu.2015.00449. eCollection 2015.
• Background Carlin BP, Louis TA. Bayesian Methods for Data Analysis, 3rd ed. 2009; Boca Raton, FL: CRC Press.
• Background Cohen JA, Coles AJ, Arnold DL, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Fisher E, Brinar VV, Giovannoni G, Stojanovic M, Ertik BI, Lake SL, Margolin DH, Panzara MA, Compston DA; CARE-MS I investigators. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1819-28. doi: 10.1016/S0140-6736(12)61769-3. Epub 2012 Nov 1.
• Background Coles AJ, Twyman CL, Arnold DL, Cohen JA, Confavreux C, Fox EJ, Hartung HP, Havrdova E, Selmaj KW, Weiner HL, Miller T, Fisher E, Sandbrink R, Lake SL, Margolin DH, Oyuela P, Panzara MA, Compston DA; CARE-MS II investigators. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012 Nov 24;380(9856):1829-39. doi: 10.1016/S0140-6736(12)61768-1. Epub 2012 Nov 1.
• Background Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency. Guideline on the clinical investigation of medicinal products for the treatment of multiple sclerosis. CHMP/771815/2011 Rev. 2. Effective date 1 October 2015.
• Background Compston A, Coles A. Multiple sclerosis. Lancet. 2008 Oct 25;372(9648):1502-17. doi: 10.1016/S0140-6736(08)61620-7.
• Background Friese MA, Fugger L. Autoreactive CD8+ T cells in multiple sclerosis: a new target for therapy? Brain. 2005 Aug;128(Pt 8):1747-63. doi: 10.1093/brain/awh578. Epub 2005 Jun 23.
• Background Goldenberg MM. Multiple sclerosis review. P T. 2012 Mar;37(3):175-84. No abstract available.
• Background Guo X, Carlin BP. Separate and joint modeling of longitudinal and event time data using standard computer packages. The American Statistician; 2004; 58, 16-24.
• Background Johnson KP, Brooks BR, Cohen JA, Ford CC, Goldstein J, Lisak RP, Myers LW, Panitch HS, Rose JW, Schiffer RB. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. The Copolymer 1 Multiple Sclerosis Study Group. Neurology. 1995 Jul;45(7):1268-76. doi: 10.1212/wnl.45.7.1268.
• Background Kampman MT, Brustad M. Vitamin D: a candidate for the environmental effect in multiple sclerosis - observations from Norway. Neuroepidemiology. 2008;30(3):140-6. doi: 10.1159/000122330. Epub 2008 Apr 2.
• Background Kappos L, Antel J, Comi G, Montalban X, O'Connor P, Polman CH, Haas T, Korn AA, Karlsson G, Radue EW; FTY720 D2201 Study Group. Oral fingolimod (FTY720) for relapsing multiple sclerosis. N Engl J Med. 2006 Sep 14;355(11):1124-40. doi: 10.1056/NEJMoa052643.
• Background Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.
• Background McCarthy DP, Richards MH, Miller SD. Mouse models of multiple sclerosis: experimental autoimmune encephalomyelitis and Theiler's virus-induced demyelinating disease. Methods Mol Biol. 2012;900:381-401. doi: 10.1007/978-1-60761-720-4_19.
• Background McKay KA, Kwan V, Duggan T, Tremlett H. Risk factors associated with the onset of relapsing-remitting and primary progressive multiple sclerosis: a systematic review. Biomed Res Int. 2015;2015:817238. doi: 10.1155/2015/817238. Epub 2015 Jan 31.
• Background National Cancer Institute (NCI); U.S. Department of health and human services, National Institutes of Health. Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. Published: May 28, 2009 (v4.03: June 14, 2010).
• Background National Multiple Sclerosis Society. Who Gets MS?. http://www.nationalmssociety.org/aboutmultiple-sclerosis/what-we-know-about-ms/who-gets-ms/index.aspx. Accessed 30 March 2016.
• Background Noonan CW, Williamson DM, Henry JP, Indian R, Lynch SG, Neuberger JS, Schiffer R, Trottier J, Wagner L, Marrie RA. The prevalence of multiple sclerosis in 3 US communities. Prev Chronic Dis. 2010 Jan;7(1):A12. Epub 2009 Dec 15.
• Background Olsson T, Boster A, Fernandez O, Freedman MS, Pozzilli C, Bach D, Berkani O, Mueller MS, Sidorenko T, Radue EW, Melanson M. Oral ponesimod in relapsing-remitting multiple sclerosis: a randomised phase II trial. J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1198-208. doi: 10.1136/jnnp-2013-307282. Epub 2014 Mar 21.
• Background Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):899-910. doi: 10.1056/NEJMoa044397.
• Background Polman CH, Reingold SC, Banwell B, Clanet M, Cohen JA, Filippi M, Fujihara K, Havrdova E, Hutchinson M, Kappos L, Lublin FD, Montalban X, O'Connor P, Sandberg-Wollheim M, Thompson AJ, Waubant E, Weinshenker B, Wolinsky JS. Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 2011 Feb;69(2):292-302. doi: 10.1002/ana.22366.
• Background Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Lancet. 1998 Nov 7;352(9139):1498-504.
• Background Rosati G. The prevalence of multiple sclerosis in the world: an update. Neurol Sci. 2001 Apr;22(2):117-39. doi: 10.1007/s100720170011.
• Background Rudick RA, Panzara MA. Natalizumab for the treatment of relapsing multiple sclerosis. Biologics. 2008 Jun;2(2):189-99. doi: 10.2147/btt.s1956.
• Background Selmaj K, Li DK, Hartung HP, Hemmer B, Kappos L, Freedman MS, Stuve O, Rieckmann P, Montalban X, Ziemssen T, Auberson LZ, Pohlmann H, Mercier F, Dahlke F, Wallstrom E. Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study. Lancet Neurol. 2013 Aug;12(8):756-67. doi: 10.1016/S1474-4422(13)70102-9. Epub 2013 Jun 11.
• Background Sormani MP, Miller DH, Comi G, Barkhof F, Rovaris M, Bruzzi P, Filippi M. Clinical trials of multiple sclerosis monitored with enhanced MRI: new sample size calculations based on large data sets. J Neurol Neurosurg Psychiatry. 2001 Apr;70(4):494-9. doi: 10.1136/jnnp.70.4.494.
• Background Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintore M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA. Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 2018 Feb;17(2):162-173. doi: 10.1016/S1474-4422(17)30470-2. Epub 2017 Dec 21.
• Background Varhaug KN, Barro C, Bjornevik K, Myhr KM, Torkildsen O, Wergeland S, Bindoff LA, Kuhle J, Vedeler C. Neurofilament light chain predicts disease activity in relapsing-remitting MS. Neurol Neuroimmunol Neuroinflamm. 2017 Nov 28;5(1):e422. doi: 10.1212/NXI.0000000000000422. eCollection 2018 Jan.
• Background Varhaug KN, Torkildsen O, Myhr KM, Vedeler CA. Neurofilament Light Chain as a Biomarker in Multiple Sclerosis. Front Neurol. 2019 Apr 5;10:338. doi: 10.3389/fneur.2019.00338. eCollection 2019.
• Background Weiner HL. Multiple sclerosis is an inflammatory T-cell-mediated autoimmune disease. Arch Neurol. 2004 Oct;61(10):1613-5. doi: 10.1001/archneur.61.10.1613. No abstract available.
• Background Zhu H, Lakkis H. Sample size calculation for comparing two negative binomial rates. Stat Med. 2014 Feb 10;33(3):376-87. doi: 10.1002/sim.5947. Epub 2013 Aug 23.

Drugs

Indications